Clinical value of Alzheimer's disease biomarker testing.

INTRODUCTION: In the Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC) study, we aimed to understand how Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing-used in medical care-impacted medical decision-making (medical utility), personal decision-making (personal utility), and health system economics. METHODS: The study was designed as an observational, longitudinal cohort study. A total of 149 patients were enrolled between February 2019 and July 2021. Patients referred to memory clinics were approached to participate if their dementia specialist ordered AD CSF biomarker testing as part of their routine medical care, and the clinical scenario met the appropriate use criteria for lumbar puncture and AD CSF biomarker testing. For the medical utility pillar, detailed clinical management plans were collected via physician questionnaires pre- and post-biomarker disclosure. RESULTS: Patients with completed management questionnaires (n = 142) had a median age of 64 (interquartile range: 59-69) years, 48% were female, and 60% had CSF biomarker profiles on the AD continuum. Clinical management changed in 89.4% of cases. AD biomarker testing was associated with decreased need for other diagnostic procedures, including brain imaging (-52.0%) and detailed neuropsychological assessments (-63.2%), increased referrals and counseling (57.0%), and guided AD-related drug prescriptions (+88.4% and -50.0% in biomarker-positive and -negative cases, respectively). DISCUSSION: AD biomarker testing was associated with significant and positive changes in clinical management, including decreased health care resource use, therapy optimization, and increased patient and family member counseling. While certain changes in management were linked to the AD biomarker profile (e.g., referral to clinical trials), the majority of changes were independent of baseline clinical presentation and level of cognitive impairment, demonstrating a broad value for AD biomarker testing in individuals meeting the appropriate use criteria for testing.

Personal value of Alzheimer's disease biomarker testing and result disclosure from the patient and care partner perspective.

INTRODUCTION: We described patients' and care partners' experiences with Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing and result disclosure in routine care. METHODS: IMPACT-AD BC is an observational study of clinic patients who underwent AD CSF biomarker testing as part of their routine medical care (n = 142). In the personal utility arm of the study, semi-structured phone interviews were conducted with a subset of patients (n = 34), and separately with their care partners (n = 31). Post-disclosure interviews were conducted ∼1 month and ∼6 months after biomarker result disclosure and investigated the patients' decision-making process around testing, impact of receiving results, wellness and lifestyle changes, and future planning. RESULTS: A majority of patients (90%) rated their decision to undergo testing as "easy." Post-disclosure, the majority (82%) reported overall positive feelings from having greater certainty and the ability to plan ahead, and results spurred them to adopt/continue healthy behaviors such as exercise (84%) and cognitive activities (54%). Care partners expressed relief from having more diagnostic certainty, increased appreciation of future caregiving responsibilities, and a desire to connect with support resources. DISCUSSION: Perspectives of persons with lived experience in dementia provide new insight into the value of biomarker testing and should be included as part of evidence-guided considerations for pre-test counseling and result disclosure. Moreover, study findings identify an interval when patients and care partners are highly receptive to positive lifestyle and medical interventions.

Exploring latent clusters in pediatric OCD based on symptoms, severity, age, gender, and comorbidity.

Given diverse symptom expression and high rates of comorbid conditions, the present study explored underlying commonalities among OCD-affected children and adolescents to better conceptualize disorder presentation and associated features. Data from 830 OCD-affected participants presenting to OCD specialty centers was aggregated. Dependent mixture modeling was used to examine latent clusters based on their age- and gender adjusted symptom severity (as measured by the Children's Yale-Brown Obsessive-Compulsive Scale; CY-BOCS), symptom type (as measured by factor scores calculated from the CY-BOCS symptom checklist), and comorbid diagnoses (as assessed via diagnostic interviews). Fit statistics favored a four-cluster model with groups distinguished primarily by symptom expression and comorbidity type. Fit indices for 3-7 cluster models were only marginally different and characteristics of the clusters remained largely stable between solutions with small clusters of distinct presentations added in more complex models. Rather than identifying a single classification system, the findings support the utility of integrating dimensional, developmental, and transdiagnostic information in the conceptualization of OCD-affected children and adolescents. Identified clusters point to the centrality of contamination concerns to OCD, relationships between broader symptom expression and higher levels of comorbidity, and the potential for complex/neurodevelopmental presentations.

Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis.

BACKGROUND: Posterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer's disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort. METHODS: We searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer's disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified using I2. FINDINGS: We identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer's Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 59·4 years (95% CI 58·9-59·8; I2=77%), 60% (56-64; I2=35%) were women, and 80% (72-89; I2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid ß in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75-87; I2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56-75; I2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90-97; I2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93-100; I2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer's disease (94%, 95% CI 90-97; I2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54-88; I2=89%), Lewy body disease (44%, 25-62; I2=77%), and cerebrovascular injury (42%, 24-60; I2=88%). INTERPRETATION: These data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer's disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity. FUNDING: None.

Cross-sectional and longitudinal neural predictors of physical activity and sedentary behaviour from a 6-month randomized controlled trial.

A sedentary lifestyle offers immediate gratification, but at the expense of long-term health. It is thus critical to understand how the brain evaluates immediate rewards and long-term health effects in the context of deciding whether to engage in moderate-to-vigorous physical activity (MVPA) or sedentary behaviour (SB). In this secondary analysis of a 6-month randomized controlled trial to increase MVPA and reduce SB among community-dwelling adults, we explored how neural activity during an executive control task was associated with MVPA and SB levels. At baseline, a subset of participants (n = 26/61) underwent task-based functional magnetic resonance imaging (fMRI) to examine neural activity underlying executive control using the Now/Later task. MVPA and SB were measured objectively using the Sensewear Mini at baseline, and 2, 4, and 6 months follow-up. We then examined the associations of baseline neural activation underlying executive control with: (1) baseline MVPA or SB; and (2) changes in MVPA and SB over 6 months. Our results determined that there is a complex neurocognitive system associated with MVPA levels, while SB appears to lack any neurocognitive control. In other words, MVPA appears to require neurocognitive effort, while SB may be the default behavioural pattern in adults.

Social Isolation, Physical Activity, and Subsequent Changes in Cognition Among Middle- and Older-Aged Adults: Results From the Canadian Longitudinal Study on Aging.

OBJECTIVE: The objectives of this study were to a) evaluate associations between social isolation and change in cognition over a 3-year period, and b) evaluate whether physical activity mediates the association between social isolation and cognition change. METHODS: Using baseline and follow-up 1 data from the Canadian Longitudinal Study on Aging, latent change score models, incorporating direct and indirect pathways, were constructed to estimate the indirect effect of social isolation on cognitive change through physical activity. Multigroup models were constructed based on age group (45-65 versus 65+ years) and sex to allow for varying estimates across age and sex. The final analytic sample included 51,338 participants. RESULTS: Indirect effects of social isolation on cognition through physical activity were evident in men and women 65+ years old for memory change ( = -0.005 [99.9% confidence interval = -0.007 to -0.002], p < .001 in both groups) and in male adults 65+ years old for executive function change ( = -0.01 [99.9% confidence interval = -0.02 to -0.006], p < .001). Statistically significant indirect effects were not observed for adults between 45 and 65 years old. CONCLUSIONS: Social isolation is associated with diminished physical activity, and in turn, diminished physical activity is associated with decline in memory in older women and men, with larger declines in executive function in older men. Public health initiatives to promote physical activity-perhaps incorporating social interaction-among older adults experiencing social isolation could be one way to mitigate the negative impact of social isolation on cognitive health.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Economic Evaluation of Exercise or Cognitive and Social Enrichment Activities for Improved Cognition After Stroke.

Importance: Cognitive impairment is prevalent in survivors of stroke, affecting approximately 30% of individuals. Physical exercise and cognitive and social enrichment activities can enhance cognitive function in patients with chronic stroke, but their cost-effectiveness compared with a balance and tone program is uncertain. Objective: To conduct a cost-effectiveness and cost-utility analysis of multicomponent exercise or cognitive and social enrichment activities compared with a balance and tone program. Design, Setting, and Participants: This economic evaluation used a Canadian health care systems perspective and the Vitality study, a randomized clinical trial aimed at improving cognition after stroke with a 6-month intervention and a subsequent 6-month follow-up (ie, 12 months). The economic evaluation covered the duration of the Vitality trial, between June 6, 2014, and February 26, 2019. Participants were community-dwelling adults aged 55 years and older who experienced a stroke at least 12 months prior to study enrollment in the Vancouver metropolitan area, British Columbia, Canada. Data were analyzed from June 1, 2022, to March 31, 2023. Interventions: Participants were randomly assigned to twice-weekly classes for 1 of the 3 groups: multicomponent exercise program, cognitive and social enrichment activities program, or a balance and tone program (control). Main Outcomes and Measures: The primary measures for the economic evaluation included cost-effectiveness (incremental costs per mean change in cognitive function, evaluated using the Alzheimer Disease Assessment Scale-Cognitive-Plus), cost-utility (incremental cost per quality-adjusted life-year gained), intervention costs, and health care costs. Since cognitive benefits 6 months after intervention cessation were not observed in the primary randomized clinical trial, an economic evaluation at 12 months was not performed. Results: Among 120 participants (mean [SD] age, 71 [9] years; 74 [62%] male), 34 were randomized to the multicomponent exercise program, 34 were randomized to the social and cognitive enrichment activities program, and 52 were randomized to the balance and tone control program. At the end of the 6-month intervention, the cost per mean change in Alzheimer Disease Assessment Scale-Cognitive-Plus score demonstrated that exercise was more effective and costlier compared with the control group in terms of cognitive improvement with an incremental cost-effectiveness ratio of CAD -$8823. The cost per quality-adjusted life-year gained for both interventions was negligible, with exercise less costly (mean [SD] incremental cost, CAD -$32 [$258]) and cognitive and social enrichment more costly than the control group (mean [SD] incremental cost, CAD $1018 [$378]). The balance and tone program had the lowest delivery cost (CAD $777), and the exercise group had the lowest health care resource utilization (mean [SD] $1261 [$1188]) per person. Conclusions and Relevance: The findings of this economic evaluation suggest that exercise demonstrated potential for cost-effectiveness to improve cognitive function in older adults with chronic stroke during a 6-month intervention.

Worsened Ability to Engage in Social and Physical Activity During the COVID-19 Pandemic and Older Adults' Mental Health: Longitudinal Analysis From the Canadian Longitudinal Study on Aging.

Background and Objectives: Restrictions implemented to mitigate the transmission of coronavirus disease 2019 (COVID-19) affected older adults' ability to engage in social and physical activities. We examined mental health outcomes of older adults reporting worsened ability to be socially and physically active during the pandemic. Research Design and Methods: Using logistic regression, we examined the relationship between positive screen for depression (10-item Center for Epidemiological Studies-Depression Scale) or anxiety (7-item Generalized Anxiety Scale) at the end of 2020 and worsened ability to engage in social and physical activity during the first 6-9 months of the pandemic among older adults in Canada. Interactions between ability to participate in social and physical activity and social participation pre-COVID (2015-2018) and physical activity were also examined. We analyzed data collected before and during the COVID pandemic from the Canadian Longitudinal Study on Aging, a nationally representative longitudinal cohort: pre-pandemic (2015-2018), COVID-Baseline survey (April to May 2020), and COVID-Exit survey (September to December 2020). Results: Of the 24,108 participants who completed the COVID-Exit survey, 21.96% (n = 5,219) screened positively for depression and 5.04% (n = 1,132) for anxiety. Worsened ability to participate in social and physical activity was associated with depression (odds ratio [OR] = 1.85 [95% confidence interval {CI} 1.67-2.04]; OR = 2.46 [95% CI 2.25-2.69]), respectively, and anxiety (OR = 1.66 [95% CI 1.37-2.02] and OR = 1.96 [95% CI 1.68-2.30]). Fully adjusted interaction models identified a buffering effect of social participation and the ability to participate in physical activity on depression (χ2 [1] = 8.86, p = .003 for interaction term). Discussion and Implications: Older adults reporting worsened ability to participate in social and physical activities during the COVID-19 pandemic had poorer mental health outcomes than those whose ability remained the same or improved. These findings highlight the importance of fostering social and physical activity resources to mitigate the negative mental health impacts of future pandemics or other major life stressors that may affect the mental health of older adults.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5,000 richly-phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Parent Management Training Augmentation to Address Coercive and Disruptive Behavior in Cognitive-Behavioral Therapy for Pediatric Obsessive-Compulsive Disorder.

Coercive and disruptive behaviors commonly interfere with cognitive-behavioral therapy (CBT) trials among youths with obsessive-compulsive disorder (OCD). Although evidence supports parent management training (PMT) for reducing disruptive behavior, no group-based PMT interventions exist for OCD-related disruptive behaviors. We studied feasibility and effectiveness of group-based adjunctive PMT among non-randomized, OCD-affected families receiving family-based group CBT. Linear mixed models estimated treatment effects across OCD-related and parenting outcomes at post-treatment and 1-month follow-up. Treatment response for 37 families receiving CBT + PMT (Mage = 13.90) was compared to 80 families receiving only CBT (Mage = 13.93). CBT + PMT was highly accepted by families. Families who received CBT + PMT had improved disruptive behaviors, parental distress tolerance, and other OCD-related outcomes. OCD-related outcomes did not significantly differ between groups. Results support CBT + PMT as effective treatment for pediatric OCD that may not provide incremental benefits beyond CBT alone. Future research should determine feasible and effective ways to incorporate key PMT components into CBT-based interventions.

Predictors of the rate of cognitive decline in older adults using machine learning.

BACKGROUND: The longitudinal rates of cognitive decline among aging populations are heterogeneous. Few studies have investigated the possibility of implementing prognostic models to predict cognitive changes with the combination of categorical and continuous data from multiple domains. OBJECTIVE: Implement a multivariate robust model to predict longitudinal cognitive changes over 12 years among older adults and to identify the most significant predictors of cognitive changes using machine learning techniques. METHOD: In total, data of 2733 participants aged 50-85 years from the English Longitudinal Study of Ageing are included. Two categories of cognitive changes were determined including minor cognitive decliners (2361 participants, 86.4%) and major cognitive decliners (372 participants, 13.6%) over 12 years from wave 2 (2004-2005) to wave 8 (2016-2017). Machine learning methods were used to implement the predictive models and to identify the predictors of cognitive decline using 43 baseline features from seven domains including sociodemographic, social engagement, health, physical functioning, psychological, health-related behaviors, and baseline cognitive tests. RESULTS: The model predicted future major cognitive decliners from those with the minor cognitive decline with a relatively high performance. The overall AUC, sensitivity, and specificity of prediction were 72.84%, 78.23%, and 67.41%, respectively. Furthermore, the top 7 ranked features with an important role in predicting major vs minor cognitive decliners included age, employment status, socioeconomic status, self-rated memory changes, immediate word recall, the feeling of loneliness, and vigorous physical activity. In contrast, the five least important baseline features consisted of smoking, instrumental activities of daily living, eye disease, life satisfaction, and cardiovascular disease. CONCLUSION: The present study indicated the possibility of identifying individuals at high risk of future major cognitive decline as well as potential risk/protective factors of cognitive decline among older adults. The findings could assist in improving the effective interventions to delay cognitive decline among aging populations.

Contributors to mental health resilience in middle-aged and older adults: an analysis of the Canadian Longitudinal Study on Aging.

OBJECTIVES: Identifying the correlates of mental health resilience (MHR)-defined as the discrepancy between one's reported current mental health and one's predicted mental health based on their physical performance-may lead to strategies to alleviate the burden of poor mental health in aging adults. Socioeconomic factors, such as income and education, may promote MHR via modifiable factors, such as physical activity and social networks. DESIGN: A cross-sectional study was conducted. Multivariable generalized additive models characterized the associations between socioeconomic and modifiable factors with MHR. SETTING: Data were taken from the population-based Canadian Longitudinal Study on Aging (CLSA), which collected data at various data collection sites across Canada. PARTICIPANTS: Approximately 31,000 women and men between the ages of 45 and 85 years from the comprehensive cohort of the CLSA. MEASUREMENTS: Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. Physical performance was measured objectively using a composite of grip strength, sit-to-stand, and balance performance. Socioeconomic and modifiable factors were measured by self-report questionnaires. RESULTS: Household income, and to a lesser extent, education were associated with greater MHR. Individuals reporting more physical activity and larger social networks had greater MHR. Physical activity accounted for 6% (95% CI: 4 to 11%) and social network accounted for 16% (95% CI: 11 to 23%) of the association between household income and MHR. CONCLUSIONS: The burden of poor mental health in aging adults may be alleviated through targeted interventions involving physical activity and social connectedness for individuals with lower socioeconomic resources.

Posterior cortical atrophy: clinical, neuroimaging, and neuropathological features.

INTRODUCTION: Posterior Cortical Atrophy (PCA) is a neurodegenerative disorder characterized by impairment of higher-order visual processing in the setting of progressive atrophy of the parietal and occipital lobes. The underlying pathology is variable but most commonly Alzheimer's disease. The majority of individuals develop symptoms before 65 years of age; however, delayed diagnosis is common due to misattribution of symptoms to ocular rather than cortical pathology. AREAS COVERED: The purpose of this review is to provide readers with an in-depth analysis of Posterior Cortical Atrophy syndrome, including clinical, imaging, pathological, and genetic features, management, and treatments. EXPERT OPINION: Most patients present initially with a relatively pure visuoperceptual-visuospatial syndrome, though other cognitive domains become affected over time. Structural neuroimaging demonstrates parieto-occipital or temporo-occipital predominant atrophy. Cerebrospinal fluid Alzheimer's disease biomarkers, or amyloid/tau PET imaging can help evaluate for underlying Alzheimer's disease, which is the most common underlying neuropathology. The cornerstone of management is focused on nonpharmacologic measures. Early etiologic diagnosis is important with the arrival of disease-modifying therapies, especially for Alzheimer's disease.

Bidirectional Associations Between Adiposity and Cognitive Function and Mediation by Brain Morphology in the ABCD Study.

Importance: Most epidemiologic studies examine the brain as an outcome in relation to adiposity (ie, the brain-as-outcome perspective), but it is also a potential risk factor associated with adiposity accumulation over time (ie, the brain-as-risk factor perspective). The bidirectionality hypothesis has not been fully explored in adolescent samples previously. Objective: To assess bidirectional associations between adiposity and cognitive function in youth and test mediational pathways through brain morphology (specifically the lateral prefrontal cortex [LPFC]), lifestyle behaviors, and blood pressure. Design, Setting, and Participants: This cohort study uses data (wave 1-3; 2 years of follow-up) from the Adolescent Brain Cognitive Development (ABCD) Study, a long-term longitudinal investigation of brain development in the United States launched in 2015, which recruited 11 878 children aged 9 to 10 years at inception. Data analysis was performed from August 2021 to June 2022. Main Outcomes and Measures: Multivariate multivariable regression analyses were used to assess bidirectional associations of indicators of cognitive function (eg, executive function, processing speed, episodic memory, receptive vocabulary and reading skills) and adiposity (eg, body mass index z scores [zBMI] and waist circumference [WC]). Mediators considered for this investigation were lifestyle variables (eg, diet and physical activity), blood pressure, and the morphology of the LPFC and its subregions. Results: A total of 11 103 individuals (mean [SD] age, 9.91 [0.6] years; 5307 females [48%]; 8293 White individuals [75%] and 2264 Hispanic individuals [21%]) were included in the current study. Multivariate multivariable regression analyses revealed that higher baseline zBMI and WC were associated with worse follow-up episodic memory (ß, -0.04; 95% CI, -0.07 to -0.01) and better vocabulary (ß, 0.03; 95% CI, 0.002 to 0.06) task performance, in covariate adjusted models. Similarly, superior baseline executive function (zBMI: ß, -0.03; 95% CI, -0.06 to -0.01; WC: ß, -0.04; 95% CI, -0.07 to -0.01) and episodic memory (zBMI: ß, -0.04; 95% CI, -0.07 to -0.02; WC: ß, -0.03; 95% CI, -0.06 to -0.002) task performance were associated with better follow-up adiposity status in covariate adjusted models. Cross-lagged panel models with latent variable modeling had a bidirectional association with executive function task performance (brain-as-outcome: ß, -0.02; 95% CI, -0.05 to -0.001; brain-as-risk factor: ß, -0.01; 95% CI, -0.02 to -0.003). The hypothesized associations were statistically mediated by LPFC volume and thickness, physical activity, and blood pressure. Conclusions and Relevance: In this cohort study, executive function and episodic memory were bidirectionally associated with adiposity indices over time in this adolescent sample. These findings suggest that the brain can be both a risk factor and an outcome of adiposity; this complex bidirectional association should be taken into account in future research and clinical practice.

Age-specific determinants of psychiatric outcomes after the first COVID-19 wave: baseline findings from a Canadian online cohort study.

BACKGROUND: Canadians endured unprecedented mental health (MH) and support access challenges during the first COVID-19 wave. Identifying groups of individuals who remain at risk beyond the acute pandemic phase is key to guiding systemic intervention efforts and policy. We hypothesized that determinants of three complementary, clinically actionable psychiatric outcomes would differ across Canadian age groups. METHODS: The Personal Impacts of COVID-19 Survey (PICS) was iteratively developed with stakeholder feedback, incorporating validated, age-appropriate measures. Baseline, cross-sectional online data collected between November 2020-July 2021 was used in analyses. Age group-specific determinants were sought for three key baseline MH outcomes: (1) current probable depression, generalized anxiety disorder, obsessive-compulsive disorder and/or suicide attempt during COVID-19, (2) increased severity of any lifetime psychiatric diagnosis, and (3) inadequate MH support access during COVID-19. Multivariable logistic regression models were constructed for children, youth (self- and parent-report), young adults (19-29 years) and adults over 29 years, using survey type as a covariate. Statistical significance was defined by 95% confidence interval excluding an odds ratio of one. RESULTS: Data from 3140 baseline surveys were analyzed. Late adolescence and early adulthood were identified as life phases with the worst MH outcomes. Poverty, limited education, home maker/caregiver roles, female and non-binary gender, LGBTQ2S + status and special educational, psychiatric and medical conditions were differentially identified as determinants across age groups. INTERPRETATION: Negative psychiatric impacts of COVID-19 on Canadians that include poor access to MH support clearly persisted beyond the first wave, widening pre-existing inequity gaps. This should guide policy makers and clinicians in current and future prioritization efforts.

Multimorbidity, COVID-19 and Mental Health: Canadian Longitudinal Study on Aging (CLSA) Longitudinal Analyses.

OBJECTIVES: This paper examines the longitudinal effects of the COVID-19 pandemic on older adults (65+) with multimorbidity on levels of depression, anxiety, and perceived global impact on their lives. METHODS: Baseline (2011-2015) and Follow-up 1 (2015-2018) data from the Canadian Longitudinal Study on Aging (CLSA), and the Baseline and Exit waves of the CLSA COVID-19 study (April-December, 2020) (n = 18,099). Multimorbidity was measured using: a) an additive scale of chronic conditions; and b) six chronic disease clusters. Linear Mixed Models were employed to test hypotheses. RESULTS: Number of chronic conditions pre-pandemic was associated with pandemic levels of depression (estimate = 0.40, 95% CI: [0.37,0.44]); anxiety (estimate = 0.20, 95% CI: [0.18, 0.23]); and perceived negative impact of the pandemic (OR = 1.04, 95% CI: [1.02, 1.06]). The associations between multimorbidity and anxiety decreased during the period of the COVID-19 surveys (estimate = -0.02, 95% CI: [-0.05, -0.01]); whereas the multimorbidity association with perceived impact increased (OR = 1.03, 95% CI: [1.01, 1.05]). CONCLUSIONS: This study demonstrates that pre-pandemic multimorbidity conditions are associated with worsening mental health. CLINICAL IMPLICATIONS: Clinicians treating mental health of older adults need to consider the joint effects of multimorbidity conditions and pandemic experiences to tailor counseling and other treatment protocols.

Walking for Cognitive Health: Previous Parity Moderates the Relationship Between Self-Reported Walking and Cognition.

BACKGROUND: Older females show greater cognitive gains from physical activity (PA) than males, which may be related to long-term consequences of female-specific reproductive events (eg, pregnancy) on cognitive health. METHODS: To determine whether previous parity could moderate the relationship between PA and cognitive decline in older women, we conducted secondary analyses of data from the Health, Aging, and Body Composition Study. We tested whether the association between average PA over 10 years and cognition (Modified Mini-Mental State Examination [3MS]) and executive functioning (digit symbol substitution test [DSST]) over 10 years varied by previous parity (nulliparity, low parity, medium parity, and grand multiparity). An analysis of covariance was performed with cognition (average and change over 10 years) as the dependent variables, parity as a categorical predictor, average PA as a continuous predictor, and a set of relevant covariates. RESULTS: Significant interactions were found between PA and parity group for all 4 comparisons: average 3MS (p = .014), average DSST (p = .032), change in 3MS (p = .016), and change in DSST (p = .017). Simple slope analyses indicated the positive relationship between PA and average 3MS and DSST was only significant in the nulliparity and grand multiparity groups, and the positive relationship between PA and change in 3MS and DSST was only significant in the grand multiparity group. CONCLUSION: The findings suggest the relationship between self-reported walking and cognitive performance was strongest in the groups at risk for cognitive decline and dementia, the nulliparous and grand multiparous groups.

Morphometry of the lateral orbitofrontal cortex is associated with eating dispositions in early adolescence: findings from a large population-based study.

Early adolescence is a critical period for eating behaviors as children gain autonomy around food choice and peer influences increase in potency. From a neurodevelopmental perspective, significant structural changes take place in the prefrontal cortex during this time, including the orbitofrontal cortex (OFC), which is involved in socially contextualized decision-making. We examined the morphological features of the OFC in relation to food choice in a sample of 10 309 early adolescent children from the Adolescent Brain and Cognitive Development Study. Structural parameters of the OFC and insula were examined for relationships with two important aspects of food choice: limiting the consumption of fast/fried food and maximizing the consumption of nutritious foods. Raw, partially adjusted and fully adjusted models were evaluated. Findings revealed that a larger surface area of the lateral OFC was associated with higher odds of limiting fast/fried food consumption in raw [odds ratio (OR) = 1.07, confidence interval (CI): 1.02, 1.12, P = 0.002, PFDR = 0.012], partially adjusted (OR = 1.11, CI: 1.03, 1.19, P = 0.004, PFDR = 0.024) and fully adjusted models (OR = 1.11, CI: 1.03, 1.19, P = 0.006, PFDR = 0.036). In contrast, a larger insula volume was associated with lower odds of maximizing healthy foods in raw (OR = 0.94, CI: 0.91, 0.97, P <0.001, PFDR = 0.003) and partially adjusted (OR = 0.93, CI: 0.88, 0.98, P = 0.008, PFDR = 0.048) models. These findings refine our understanding of the OFC as a network node implicated in socially mediated eating behaviors.